1. Field of the Invention
The present invention relates to a microdroplet or microparticle with Janus or core-shell internal morphology including N-isopropylacrylamide (NIPAAm) as a single component. More particularly, the present invention relates to a microdroplet or microparticle with Janus or core-shell internal morphology, which is obtained under the control of phase separation of high-concentration NIPAAm formed in a microfluidic device.
2. Discussion of Related Art
To facilitate drug delivery all over the world and improve a therapeutic effect, there is an increasing interest in development of microparticles having a small size and an excellent effect. Currently, a drug is delivered through a route of visible administration, for example, oral, intravenous, or cutaneous administration. Since use of a microparticle enables delivery of a target drug to an accurate site, effects of the drug may be maximized. However, conventional microparticles have limits of performance and functions since they have one space in the center thereof to be filled with a drug or a physiologically active material. For example, when at least two drugs have to be added to one microparticle, the drugs react with each other to show a medicinal effect before they are delivered to a desired site, which makes it difficult to control release of the drugs.
With regard to the microparticle, a hydrogel refers to a hydrophilic polymer forming a 3-dimensional network structure through a chemical or physical bond. A hydrogel may absorb a large amount of water in the polymer since it is highly hydrophilic. Here, an amount of water to be absorbed into the hydrogel may be determined according to chemistry of the polymer, a degree of hydrophilicity, and a level of crosslinking between polymer chains. In particular, the hydrogel has been widely used as a biomedical material since it has highly similar characteristics to in vivo cellular tissues, and thus exhibits few side effects even when it is inserted into a human body.
In recent years, there has been an increasing amount of research conducted to develop a hydrogel whose physical properties are altered by a reaction with external stimuli such as temperature, pH, light, a magnetic force, etc. Among these, poly-N-isopropylacrylamide (poly-NIPAAm) obtained by crosslinking NIPAAm is a representative temperature-sensitive hydrogel in which volume shrinkage and surface characteristics are caused at a temperature of 32° C., similar to body temperature.
In particular, Professor Okabe (Japan) reported solubility transition and phase separation taking place in high-concentration NIPAAm in 2010 (J. Phys. Chem. B 2010, vol. 114, 14995-15002). When a high concentration of NIPAAm is dissolved in water at 25° C. or more, at least two phases, that is, an H phase and an L phase, are formed due to solubility transition. It was reported that both the H and L phases include NIPAAm as a basic component material, but are not miscible with each other, and NIPAAm is present at a relatively higher concentration in the H phase, compared with the L phase.
Methods of preparing a hydrogel microparticle known in the related art include physical methods such as emulsification, coacervation, and spray drying, and chemical methods such as heterogeneous polymerization. With the development of microfluidic technology, there has been much research conducted on microfluidic devices to prepare various microdroplets/microparticles including a hydrogel microdroplet/microparticle. In this case, the microdroplet/microparticle prepared in the microfluidic device has advantages in that it may be formed with a uniform size, and its size may be easily controlled.
In spite of the advantages of the microfluidic device, however, preparation of a hydrogel microparticle using a conventional microfluidic device has been restricted to preparation of the hydrogel microparticle into a single phase. Since components of a fluid composed of a single phase are mixed by means of diffusion or stirring, a boundary is not clear in the structure of a finally prepared microdroplet/microparticle.
That is, to prepare a microdroplet/microparticle having a clear boundary, two fluids which are not mixed with each other should be used as dispersed phases, and another fluid which is not mixed with the two fluids should be used as a continuous phase. However, when a dispersed phase is composed of two fluids which are not mixed, different component materials should be selected for each fluid. As a result, it is impossible to obtain a particle composed of a single material.
Even when each of two fluids in the dispersed phase is composed of a single material, the two fluids are mixed due to diffusion caused by a difference in concentration between two dispersed phases, or undesirable disturbance caused by a continuous phase, which makes it difficult to prepare a microdroplet/microparticle having a divided clear boundary.